Submission Number: TER-4-35-36
Abstract Number: 402
EFFECTS OF ESTROGEN RECEPTOR (ER) ANTAGONIST ICI 182,780 (ICI) ON LOCAL UTERINE BLOOD FLOW (UBF) RESPONSES TO SYSTEMIC ESTRADIOL-17 (E2).
Terrance M Phernetton 1, Ian M Bird 1, Dong Bao Chen* 1 and Ronald R Magness* 1,2
Perinatal Research Labs, Depts Ob/Gyn, Univ Wisconsin-Madison Medical School, Meriter Hospital, Madison, WI 1
Animal Sciences, University of Wisconsin, Madison, WI 2
E2 increases UBF, via a NO-mediated mechanism and elevates uterine artery endothelial (UAendo) eNOS. We tested the hypothesis that there is a population of ER in UAendo and that unilateral infusion of ICI, a specific ER antagonist, will locally inhibit the E2-mediated increases in UBF. Methods: ER protein expression in UAendo was evaluated by Western analysis (n=2 ewes). Six ewes were ovariectomized and instrumented with Transonic flow probes around the UA and catheters placed in small branches of UA. Ewes were given E2 (1 g/kg) IV on three separate days to establish steady uterine responses. For each experiment, baseline systemic (mean arterial pressure and heart rate) and UBF were continuously monitored for 2.5 hours, starting 30 min prior to Vehicle or ICI infusion into one UA 10 min before and 40 min after 1 g/kg IV E2. Doses of ICI (0.1, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 g/min) and the infusion side were randomized and bracketed by E2/Vehicle responses every 2-3 days to insure stability of the UBF response. Results: ER protein was expressed in UAendo at the expected molecular weight (67kD), corresponding to a human recombinant ER standard. For physiological studies, similar control UBF responses to E2 were observed to both uterine sides; i.e. systemic E2 increased unilateral UBF from 101 to 1136 ml/min (P<0.01) at 90-120 min (10-13 fold increase). Unilateral ICI infusion time and dose dependently reduced ipsilateral UBF responses to systemic E2, with maximal inhibition of 555.7% (90-120 min) with doses between 2.5-3.0 ug/min (P<0.01). In contrast, contralateral UBF responses to systemic E2 remained unaffected by locally administered ICI. ICI did not significantly alter either mean arterial pressure or heart rate with or without E2. Conclusion: UA endothelium expresses ER and E2 locally increases UBF via a specific ER-mediated mechanism. Support: NIH HL49210,HL57653,HD33255, & HL56702. .
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